AB1315 SARILUMAB IN PATIENTS WITH REFRACTORY GRAVES’ ORBITOPATHY. EFFECTIVENESS AND SAFETY IN A SERIES OF CASES IN CLINICAL PRACTICE.
Authors: V. Moreira Navarrete, F. J. Toyos Sáenz de Miera, A. M. Garrido Hermosilla, P. Muñoz Reinoso, M. J. Madrigal Domínguez, J. J. Pérez Venegas
Journal: Annals of the Rheumatic Diseases (2022)

Background Graves’ orbitopathy (GO) is an autoimmune disease of the retroocular tissues that occurs in patients with Graves’ disease. Tocilizumab (TCZ), an interleukin (IL)-6 inhibitor has been used in patients with glucocorticoid (GC)-resistant Graves’ orbitopathy with good results. We have previously reported results obtained in 15 OG patients treated with TCZ where a decrease in mean CAS from 4.9 to 1.7 was observed. Sarilumab, another IL-6 inhibitor, is indicated for the treatment of rheumatoid arthritis and has been used in other pathologies as an off-label use, similar to TCZ, on the grounds that they share a common mechanism of action. Objectives To analyse the effectiveness of Sarilumab treatment in patients with GC-resistant OG in routine clinical practice. Methods A descriptive retrospective observational study of a series of patients with moderate-severe active OG on Sarilumab treatment was performed. Medical records of patients who had received at least 1 cycle of Sarilumab treatment were reviewed. Demographic and disease data were collected. Effectiveness was assessed by CAS (Clinical Activity Score) reduction before and at 3-6 months of treatment. A reduction of CAS≥ 2 points together with obtaining inactivity (CAS &lt; 3) was considered a favourable response. The study was approved by Research Ethics Committee. Results In the rheumatology department of the Hospital Virgen Macarena, 25 patients were treated with IL-6 inhibitors, 20 with tocilizumab and 5 with Sarilumab. Five patients were included, 2 women and 3 men, with a mean age of 43 years. All but one had bilateral ocular involvement. 2 patients were active smokers, 1 ex-smoker and 2 non-smokers. Two patients were diabetic, none of them had retinopathy. The mean time of disease until their evaluation in Rheumatology was 3.5 years. All had been treated with antithyroid drugs, 1 with Radioiodine and one patient had undergone thyroidectomy. 100% of patients had an active moderate-severe orbitopathy, all had been treated with local measures, 3 with selenium and none had undergone rehabilitative surgery. Three patients had been on at least one course of intravenous steroids. Patients received Sarilumab at a dose of 200 mg subcutaneous injection every 15 days for a mean of 11 months (range 7-21 months), 100% in monotherapy. The mean initial CAS was 5/7 and the final CAS was 2.75/10. The CAS score was reduced by 3 points on average. 100% had a favourable response and achieved inactivity, also reducing the severity of the disease. Furthermore, there was an improvement in thyroid function parameters and a reduction in antibody titters against TSH receptor and anti-thyroid peroxidase. All patients were continuing treatment except for one patient who had discontinued treatment due to clinical remission. No adverse events were recorded except for mild neutropenia in one patient, which did not require dose reduction. No patient required subsequent immunosuppressive treatment or surgery. Conclusion Sarilumab treatment in patients with moderate-severe active OG appears to be an effective and safe therapeutic alternative, clinically similar to that obtained with TCZ in our series. This is the first published series of Sarilumab use in OG patients. References [1]Bartalena L, Kahaly GJ, Baldeschi L, et al. THE 2021 EUROPEAN GROUP ON GRAVES’ ORBITOPATHY (EUGOGO) CLINICAL PRACTICE GUIDELINES FOR THE MEDICAL MANAGEMENT OF GRAVES’ ORBITOPATHY. Eur J Endocrinol. 2021; EJE-21-0479.R1. doi: 10.1530/EJE-21-0479. [2]Sánchez-Bilbao L, Martínez-López D, Revenga M, et al. Anti-IL-6 Receptor Tocilizumab in Refractory Graves’ Orbitopathy: National Multicenter Observational Study of 48 Patients. J Clin Med. 2020;9(9):2816. [3]L. Fernández-Fuente-Bursón, F.J.Toyos-Sáenz-Miera, M.D. Ruiz-Montesino, et al. EFECTIVIDAD DEL TRATAMIENTO CON ANTI-INTERLEUCINA 6 SUBCUTÁNEA EN PACIENTES CON ORBITOPATÍA DE GRAVES MODERADA-GRAVE ACTIVA REFRACTARIA A TERAPIA CONVENCIONAL. Poster presented at the congress: 36º Congreso Nacional Sociedad Española de Reumatología; 2020 Oct 20-24; virtual. Disclosure of Interests None declared